Triploidy

Question 1

What is triploidy?

Answer 1

• Chromosomal anomaly seen in 1 - 2% of all conceptions and ~10% of spontaneous abortions
• 69,XXX or 69,XXY
• Most triploid conceptions end in the first trimester as spontaneous abortions, some reports of live births, with the longest reported survival of 10.5 months

Question 2

Digyny

Answer 2

• Extra set of chromosomes = maternal
• Associated with asymmetric severe fetal growth restriction (FGR), pronounced wasting of body and sparing of head, normal NT-thickness and very low serum free beta-hCG & PAPP-A, and a very small placenta
• Usually occurs as a result of errors in meiosis I or meiosis II during oogenesis

Question 3

Diandry

Answer 3

• Extra set of chromosomes = paternal
• Placenta = enlarged & partially molar
• Fetus = symmetric mild growth restriction or well grown fetus
• Fetal NT = high
• Maternal serum free beta-hCG = 10X higher than normal
• Diandric triploidy can also cause sever maternal complications, including severe early-onset preeclampsia and choriocarcinoma

Question 4

Molar pregnancy

Answer 4

• When a non-viable fertilized egg implants in the uterus
• Can be complete or partial
• Tissue that normally would become a fetus instead becomes an abnormal growth in the uterus
• This growth triggers symptoms of pregnancy (occasionally RARE pregnancy that is though to be twins, one is molar and one is a real fetus)

Question 5

Complete mole

Answer 5

• When either a single sperm or two sperm combine with an “empty” egg (without either a maternal nucleus or without maternal DNA)
• The sperm then reduplicates and forms a 46 chromosome set
• The tissue grows and looks similar to a cluster of grapes. It does not have fetal tissue.

Question 6

Partial mole

Answer 6

2/3 of time: Two sperm fertilize an egg (dispermy) yielding paternal triploidy genotype –> results in abundant trophoblast and poor embryonic development

1/3 of time: Sperm fertilizes a diploid egg, yielding maternal triploidy genotype –> results in retardation of embryonic development and a small fibrocytic placenta

Question 7

Risk factors for molar pregnancy

Answer 7

• Age >35
• Hx of molar pregnancy; especially 2 or more
• Hx of miscarriage
• Diet low in carotene (form of vitamin A) (women low in vitamin A have an increased rate of complete molar pregnancy)
• Certain ethnic groups (Filipinos)

Question 8

Invasive Mole

Answer 8

• A hydatidiform mole that grew into the muscle layer of the uterus, can develop from complete or partial moles (more often complete)
• May spread to other parts of the body such as the vagina vulva and lung

Question 9

Choriocarcinoma

Answer 9

malignant gestational trophoblastic cancer, usually of the placenta

Question 10

Possible forms of inherited triploidy

Answer 10

There have been some reports of autosomal recessive triploidy and a susceptibility locus has been assigned to chromosome 19.

Question 11

What method of NIPT would possibly pick up a case of triploidy?

Answer 11

DIANDRIC ORIGIN ONLY: Only the lab Natera, which uses targeted amplification and analysis of SNPs on chromosomes 21, 18, 13, X and Y in one reaction and determines the chromosomal copy number (cannot distinguish between twins and triploidy by this test alone)

Every other lab uses a counting method where the amounts of chromosomes 21, 18,13, X and Y are compared against other chromosome amounts as a reference and thus would not pick up triploidy.

Question 12

Low fetal fraction on NIPT (through Natera), multiple congenital anomalies, and fetal growth restriction would be indicative of _________________

Answer 12

Digynic triploidy.

This is most likely due to the associated small placental mass.

Question 13

If you have 2 maternal copies of a genome only, what kind of tissue would develop?

Answer 13

Fetal tissue only, “benign cystic teratoma”

Question 14

With 2 paternal copies of a genome only, what kind of tissue would develop?

Answer 14

Placental tissue, no fetal tissue

Question 15

Hydatidiform mole

Answer 15

Clump of growing tissue